The preparation of piperazines and various derivatives thereof by cyclization reactions, some of which are vapor phase processes is known in the art. Generally speaking processes known for the manufacture of N,N'-disubstituted piperazines have been characterized by one or more disadvantages such as requiring expensive starting materials or requiring high pressure reaction conditions, or obtaining low yields. The preparation of N-substituted piperazines from inexpensive starting materials in good yields and at mild conditions does not appear previously taught.
The process set forth in U.S. Pat. No. 3,067,199 discloses the use of alkanolamines heated in the presence of a nickel or cobalt hydrogenation/dehydrogenation catalyst to produce alkyl-substituted piperazines and alkyl-substituted pyrazines.
One of the earlier patents in this area teaches the preparation of dimethylpiperazine by subjecting the vapors of a compound from the group consisting of a methylated tetraethylenepentamine or a lower methylated linear member (monomer, dimer or trimer) of the ethylene diamine family to a silica-alumina cracking catalyst at a temperature of about 600.degree.-700.degree. F. (See U.S. Pat. No. 3,029,240)
In U.S. Pat. No. 3,037,025 a method of producing N-alkyl-substituted piperazines is revealed which permits a broad choice of raw materials to be used and allows the production of a relatively high proportion of the valuable N-monosubstituted piperazines as compared to the preparation of N,N'-disubstituted piperazines. The reactant compound is represented by the formula: ##STR1## wherein Z and Z' are selected from the group consisting of hydrogen and lower alkyl radicals. X represents a radical selected from the group consisting of OH, NH.sub.2 and ##STR2## in which Z and Z' have the values noted above, with an alkanol represented by the formula ROH in which R is an alkyl radical. This compound is reacted in the presence of hydrogen and a hydrogenation catalyst. In this reference, with the temperature around 250.degree. C., the best yield of N,N'-dimethylpiperazine was about 16%.
In U.S. Pat. No. 3,120,524 N-monoalkyl-substituted piperazines are prepared in one step by contacting an amine with a hydrogenation catalyst in the presence of hydrogen at a temperature around 250.degree. C., said amine being represented by the formula: ##STR3## wherein R represents a lower alkyl radical and Z and Z' are selected from the group consisting of hydrogen and a lower alkyl. The yield of N,N'-disubstituted piperazines was under 10%.
U.S. Pat. Nos. 3,037,025 and 3,120,524 describe techniques where low yields of N,N'-dialkylpiperazines are obtained using temperatures in the range of 250.degree. C. and pressures close to 500 psig.
U.S. Pat. No. 3,647,795 discloses a process for cyclodehydration of N-substituted ethanolamine to produce N,N'-disubstituted piperazine by passing the vapors of said N-substituted ethanolamine over an activated alumina catalyst at high temperatures of 500.degree.-700.degree. F. The ability to selectively cyclohydrate N-substituted ethanolamines at atmospheric pressure was a novel feature. The yields of N,N'-dialkylpiperazines range from 30-70%.
U.S. Pat. No. 3,067,199 relates to a method for preparing alkyl-substituted piperazines and alkyl-substituted pyrazines with high conversions and high yields by heating an alkanolamine in the presence of a nickel or cobalt hydrogenation/dehydrogenation catalyst. The preferred temperature range was 130.degree.-240.degree. C. and the preferred pressure range was 200-1200 psig. The yields were as high as 70-85%.
Tomalia et al. disclose a process for preparing 1,4-disubstituted piperazines by contacting a basic catalytic aziridine with sulfur dioxide in the presence of a catalytic amount of iodide ion. (See U.S. Pat. No. 3,697,524)
In Tetrahedron Letters, Vol. 27, No. 3, pp. 377-380, 1986, Watanabe discloses the reaction of N-methylaniline with ethylene glycol in the presence of a homogeneous ruthenium catalyst to provide a 51% yield of 1-methylindole. He also reported that: ##STR4##
In many of the references found in the art the substituted piperazines are formed by reacting vapors at high pressures and temperatures. None of the references found used common, inexpensive reactants to make N,N'-disubstituted piperazines. In most of the reactions, mild conditions were not sufficient to bring about good yields.
It would be an advance in the art if N-substituted piperazines could be prepared in good conversion and yield under mild conditions from relatively inexpensive starting materials.